In all tissues and organs there are arachidonate metabolizing systems which can be triggered by both physiological and pathological events. Since these metabolites are highly active and are incompletely known it is important to identify their actions and relationships. This information permits us to manipulate the pathways to enhance or minimize release of the metabolites. In this manner we hope to reduce or ameliorate pathological procedures underlying cardiovascular-renal disease. We are particularly focusing on safe and well established drugs in order to develop new methods of treatment. Our research goals include: (1) Further manipulation of the cardiovascular effect of arachidonate with intra- as well as extracellular calcium antagonists, (2) developing more specific prostaglandin receptor antagonists active in vivo on the cardiovascular system, (3) further definition of the role of corticosteroids by extending our studies to its effect in modifying arachidonate and prostaglandin mediated changes in blood pressure and mortality, (4) to synthesize sufficient authentic prostaglandin endoperoxides and thromboxane A2, (5) to develop the whole blood aggregometer, and (6) to further define the developmental changes in the vascular responses to the prostaglandins in the neonatal period.